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The purpose of the present study was to analyse the impact of melatonin on the phosphorylated transcription factor cAMP\u2010response element\u2013binding protein (pCREB). In pancreatic rat insulinoma \u03b2\u2010cells (INS\u20101), pCREB immunofluorescence intensities in cell nuclei using digitised confocal image analysis were measured to semi\u2010quantify differences in the pCREB immunoreactivity (pCREB\u2010ir) caused by different treatments. Increasing concentrations of forskolin or 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX) resulted in a dose\u2010dependent rise of the mean fluorescence intensity in pCREB\u2010ir nuclear staining. Concomitant melatonin application significantly decreased pCREB\u2010ir in INS\u20101 cells after 30\u2010min, 1\u2010hr and 3\u2010hr treatment. The melatonin receptor antagonists luzindole and 4\u2010phenyl\u20102\u2010propionamidotetraline (4P\u2010PDOT) completely abolished the pCREB phosphorylation\u2013decreasing effect of melatonin, indicating that both melatonin receptor isoforms (MT<jats:sub>1<\/jats:sub> and MT<jats:sub>2<\/jats:sub>) are involved. In a transfected INS\u20101 cell line expressing the human MT<jats:sub>2<\/jats:sub> receptor, melatonin caused the greatest reduction in pCREB after IBMX treatment compared with nontransfected INS\u20101 cells, indicating a crucial influence of melatonin receptor density on pCREB regulation. Furthermore, the downregulation of pCREB by melatonin is concomitantly associated with a statistically significant downregulation of Camk2d transcript levels, as measured after 3\u2003hr. In conclusion, the present study provides evidence that the phosphorylation level of CREB is modulated in pancreatic \u03b2\u2010cells by melatonin. Mediated via CREB, melatonin regulates the expression of genes that play an important functional role in the regulation of \u03b2\u2010cell signalling pathways.<\/jats:p>","DOI":"10.1111\/j.1600-079x.2012.01004.x","type":"journal-article","created":{"date-parts":[[2012,4,18]],"date-time":"2012-04-18T18:14:35Z","timestamp":1334772875000},"page":"344-357","source":"Crossref","is-referenced-by-count":25,"title":["Phosphorylation of cyclic AMP\u2010response element\u2013binding protein (CREB) is influenced by melatonin treatment in pancreatic rat insulinoma \u03b2\u2010cells 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